To date chromosome studies on drug abuse subjects have been limited to the identification and evaluation of unstable chromosome alterations. It is now possible to also investigate stable chromosome alterations, variations in chromosome repair processes as well as changes in cellular protein fractions to monitor at the cytogenetic and biochemical levels the detection of low levels of mutagenic sensitivity. A regimen of these procedures will be employed in this project to identify and specify any increase of methadone maintenance. The study will be conducted on the leukocytes of human, non-human primates and rats exposed to opiates including methadone as compared with matched controls. Chromosome alterations before and after the start of methadone maintenance will be investigated by standard cytogenetic procedures, sequential chromosome banding studies, sister chromatid exchange analyses, as well as biochemical examination of DNA repair processes (including photo-reactivation, excision repair and post replication repair) and alterations in protein synthesis.